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Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery

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A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 8867

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Dr. Stamatios N. Katsimperis

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Guest Editor

2nd Department of Urology Sismanoglio General Hospital, University of Athens, Athens, Greece
Interests: urology

Dr. Lazaros Tzelves

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Guest Editor

2nd Department of Urology, National and Kapodistrian University of Athens, Sismanogleion Hospital, 11526 Athens, Greece
Interests: urolithiasis; robotic surgery; prostate cancer; kidney cancer; bladder cancer
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Special Issue Information

Dear Colleagues,

This Special Issue will focus on recent innovations and clinical advances in prostate cancer, spanning early detection, risk stratification, novel imaging modalities, minimally invasive and robotic surgical techniques, and the integration of molecular biomarkers into personalized treatment strategies. Emphasis will be placed on multidisciplinary approaches and the evolving role of artificial intelligence and genomics in clinical decision making.

For this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

Prostate cancer;
Precision medicine;
Molecular biomarkers;
Risk stratification;
Robotic surgery;
Artificial intelligence;
Genomics;
Personalized treatment;
Imaging modalities;
Multidisciplinary approach.

We look forward to receiving your contributions.

Dr. Stamatios N. Katsimperis
Dr. Lazaros Tzelves
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

prostate cancer
precision medicine
molecular biomarkers
risk stratification
robotic surgery
artificial intelligence
genomics
personalized treatment
imaging modalities
multidisciplinary approach

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Published Papers (7 papers)

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Research

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16 pages, 4607 KB

Open AccessArticle

External Validation and Clinical Impact of the Barcelona Predictive Models for Detecting Significant Prostate Cancer in Prostate Biopsies in an Ibero-American Population

by Nahuel Paesano, Juan Camean, Maximiliano Ringa, Maximiliano López-Silva, Guido Koren, Tomás Eduardo Olmedo, Joaquín Ignacio Gurovich, Edgar Iván Bravo-Castro, Violeta Catalá, Pablo Contreras, Juan Justo-Quintas, José Miguel Pérez-Ruiz, Silvia García-Barreras, Berta Miró, Lucas Regis, Olga Méndez, Enrique Trilla and Juan Morote

Cancers 2026, 18(11), 1810; https://doi.org/10.3390/cancers18111810 - 1 Jun 2026

Cited by 1 | Viewed by 582

Abstract

Objectives: To externally validate the Barcelona Predictive Models (BCN-PM 1 and 2) for detecting csPCa in an Ibero-American population. BCN-PM 1 was designed to reduce magnetic resonance imaging (MRI) use, whereas BCN-PM 2 aims to decrease unnecessary prostate biopsies. Methods: This prospective, multicenter study included 661 men with suspected PCa recruited in 2025 across three Ibero-American centers. All participants underwent MRI followed by targeted biopsies of lesions with the Prostate Imaging–Reporting and Data System (PI-RADS) ≥ 3, along with systematic biopsy. When PI-RADS lesions were <3, only systematic biopsies were performed. CsPCa was defined as International Society of Urological Pathology Grade Group ≥ 2. BCN-PM 1 incorporates age (years), family history of PCa (no vs. yes), prior negative prostate biopsy (no vs. yes), digital rectal examination (DRE: normal vs. suspicious), and prostate volume-derived estimation by DRE (small, median, or large). BCN-PM 2 includes age, family history of PCa, prior negative prostate biopsy, prostate volume measured by MRI (mL), and PI-RADS score (1–5). Results: The rate of csPCa detection was 53.7%. Both models demonstrated good calibration with strong agreement between predicted probabilities and observed csPCa rates. BCN-PM 1 closely followed the reference line, with minor deviations at higher predicted probabilities, whereas BCN-PM 2 showed modest departures at the extremes of risk. The area under the curve was 0.740 (95% CI 0.702–0.777) for BCN-PM 1 and 0.803 (95% CI 0.769–0.836) for BCN-PM 2 (p < 0.001). Decision curve analysis demonstrated a net benefit for both models compared with strategies of biopsy in all or no men. BCN-PM 2 showed greater net benefit than BCN-PM 1. At 95% sensitivity, BCN-PM 1 reduced MRI requests by 10.6%, while BCN-PM 2 avoided 19.4% of unnecessary biopsies. The sequential use of BCN-PM 1 and 2 resulted in a 10.6% reduction in MRI exams and a 23.1% reduction in biopsies, at the cost of missing 8.4% of csPCa cases. The performance of the biopsy improved from 53.7% to 64.0% (p < 0.001). Conclusions: BCN-PM1 and BCN-PM 2 were successfully validated in an Ibero-American population. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery)

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33 pages, 2164 KB

Open AccessArticle

Clinically Significant ISUP Upgrading in the Multiparametric MRI Era: Biopsy Tumor Burden Outperforms Complex Machine Learning Models in a Single-Center Exploratory Cohort

by Cristian Condoiu, Adelina Baloi, Dorel Sandesc, Alin Adrian Cumpanas, Silviu Latcu, Vlad Dema, Radu Caprariu, Alina Cristina Barb, Andreea Ciucurita, Adelina Marinescu, Talida Georgiana Cut and Razvan Bardan

Cancers 2026, 18(5), 730; https://doi.org/10.3390/cancers18050730 - 24 Feb 2026

Cited by 2 | Viewed by 1037

Abstract

Background/Objectives: Despite multiparametric MRI (mpMRI)-guided biopsy, clinically significant upgrading (CSU) of ISUP Grade Group (GG) at radical prostatectomy (RP) remains common in prostate cancer (PCa). We aimed to identify predictors of CSU (biopsy GG ≤ 2 to RP GG ≥ 3) using routine preoperative variables, and to benchmark a parsimonious logistic model against multiple machine learning (ML) classifiers. Methods: In this single-center exploratory analysis, 96 consecutive PCa patients underwent pre-biopsy mpMRI, systematic ± MRI-targeted biopsy, and RP. Predictive modeling was restricted to biopsy GG 1–2 patients (n = 64). LASSO-guided feature selection and Firth-penalized logistic regression were used to build a locked reference model, evaluated against ML classifiers using cross-validated discrimination, calibration, and decision curve analysis. Results: CSU occurred in 10/64 patients (15.6%). Positive core ratio was the dominant independent predictor (adjusted OR 1.54 per 10% increase, 95% CI 1.10–2.17). PSA density (PSAD) showed a consistent positive association but did not retain independent significance. The locked two-variable model (AUC ≈ 0.75–0.79) outperformed all ML classifiers in discrimination, calibration, and net clinical benefit; however, the limited event count (n = 10) constrains model stability, and these findings require external validation. Conclusions: In a PCa mpMRI-informed diagnostic pathway, CSU is primarily driven by biopsy tumor burden. A simple logistic model based on positive core ratio and PSAD outperformed more complex ML approaches in this exploratory cohort, supporting integration of biopsy tumor burden metrics into preoperative risk stratification pending external validation. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery)

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16 pages, 1199 KB

Open AccessArticle

Neoadjuvant ADT for Asian Patients Undergoing Robotic Radical Prostatectomy Is the Conversation Over?—A Propensity-Matched Comparison

by John Joson Ng, Sean Lim, Alvin Lee, Yu Guang Tan, Kae Jack Tay, Henry Ho, John Yuen and Kenneth Chen

Cancers 2026, 18(4), 661; https://doi.org/10.3390/cancers18040661 - 18 Feb 2026

Viewed by 979

Abstract

Background: Evidence for neoadjuvant androgen deprivation therapy (ADT) before radical prostatectomy (RP) remains inconclusive, and current guidelines do not endorse its routine use. Objective: We aimed to evaluate the impact of neoadjuvant ADT on surgical and oncologic outcomes in a Singaporean cohort undergoing radical prostatectomy. Design, setting, and participants: In this retrospective study, 1091 men underwent RP between 2013 and 2024; a total of 105 received neoadjuvant ADT and 986 did not. A 1:1 propensity score-matched analysis was performed on age, PSA, PSA density, Gleason score, clinical T-stage, and receipt of adjuvant therapies, yielding 105 matched pairs. Outcome measurements and statistical analysis: The primary outcome was biochemical recurrence (BCR). Secondary surgical outcomes included operative time, estimated blood loss, length of stay, catheter duration, and postoperative complications. Secondary oncologic outcomes included extracapsular extension, margin status, seminal vesicle invasion, lymph node involvement, clinical-to-pathological T-stage downstaging, Gleason score decrease, and PSA decrease. Kaplan–Meier survival and univariable linear and logistic regression analyses were used. Subgroup analysis was performed using stratified odds ratios to identify clinical subgroups that derived the greatest benefit from neoadjuvant ADT in terms of biochemical recurrence reduction. Results and limitations: After matching, neoadjuvant ADT was associated with a lower rate of extracapsular extension (30.8% vs. 51.4%, p = 0.004), positive surgical margins (18.4% vs. 39.4%, p = 0.002), lymph node involvement (1.0% vs. 13.0%, p = 0.002), and biochemical recurrence (4.8% vs. 18.1%, p = 0.005). There were no significant differences in operative time, blood loss, length of stay, or complication rates. Before matching, 2-year biochemical recurrence-free survival (BCR-FS) did not differ significantly (93.0% vs. 88.2%, log-rank p = 0.26), but after matching, BCR-FS favored ADT (93.0% vs. 81.8%, log-rank p = 0.02). Subgroup analysis showed that the reduction in biochemical recurrence with neoadjuvant ADT was more pronounced in patients with PSA density ≥ 0.20 ng/mL², Gleason score ≥ 8, and clinical T3 disease. Limitations include the retrospective design and potential residual confounding. Conclusions: Neoadjuvant ADT prior to RP significantly reduces locoregional spread and biochemical recurrence without increasing perioperative morbidity. Prospective trials are needed to confirm its benefit in high-risk prostate cancer. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery)

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Review

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28 pages, 1604 KB

Open AccessReview

Deciphering the Heterogeneity of Cancer-Associated Fibroblasts in Prostate Cancer: From Stromal Biology to Clinical Translation

by Ho Trong Tan Truong, Whi-An Kwon, Hyeong Jung Woo, Minseok S. Kim, Nhu Quang Tran and Jae Young Joung

Cancers 2026, 18(10), 1600; https://doi.org/10.3390/cancers18101600 - 14 May 2026

Cited by 1 | Viewed by 736

Abstract

Prostate cancer (PCa) progression and treatment resistance are driven by tumor-intrinsic mechanisms and adaptive remodeling of the tumor microenvironment, in which cancer-associated fibroblasts (CAFs) play a crucial role. Although CAF biology is increasingly recognized, a major translational gap remains: CAFs are highly heterogeneous, and comprise distinct functional states with divergent effects on disease progression, immune regulation, and therapeutic resistance. To bridge this gap, we synthesize evidence from single-cell and spatial transcriptomic studies, tissue-based pathology, liquid biopsy assays, and molecular imaging to construct an evidence-tiered, decision-oriented translational framework that connects stromal mechanisms, translational measurement strategies, and therapeutic interventions in PCa. Single-cell and spatial transcriptomic analyses have consistently identified multiple CAF programs, including matrix-remodeling, inflammatory, immunoregulatory, antigen-presenting, and therapy-imprinted states, each with distinct functional outputs and clinical correlates. Tissue-based readouts, including reactive stromal grade (RSG) and fibroblast activation protein (FAP) immunohistochemistry, provide practical proxies for stromal activation and correlate with disease-specific mortality and imaging phenotypes. Circulating CAFs (cCAFs) represent an emerging liquid biopsy modality for longitudinal stromal monitoring, although technical standardization is required before clinical implementation. FAP-targeted PET imaging and emerging dual prostate-specific membrane antigen (PSMA)/FAP-targeted theranostic strategies provide noninvasive tools for patient selection and response assessment, particularly in PSMA-discordant or tracer-heterogeneous disease. Androgen receptor (AR)-targeted therapy can reprogram stromal states toward resistance-promoting circuits, highlighting the dynamic and plastic nature of the CAF compartment. A state-based CAF framework organizes stromal biology into testable translational hypotheses rather than immediate clinical standards. RSG and FAP-based tissue or imaging readouts are practical markers of stromal activation, whereas spatial CAF-immune signatures and cCAF assays remain investigational and require assay harmonization and prospective validation. Future trials should pre-specify stromal biomarkers as enrichment or pharmacodynamic variables when matched to the intervention and should avoid treating CAFs as a uniform therapeutic target. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery)

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25 pages, 1930 KB

Open AccessReview

The HGF/MET Axis in Advanced Prostate Cancer: From Context-Dependent Biology to Biomarker-Driven Therapeutic Strategies

by Filippos Koinis, Maria Smaragdi Vlachou, Georgios Nintos, Georgios Christodoulopoulos, Emmanouil Panagiotidis, Ioannis Eleftheropoulos, Galatea Kallergi, Michail Samarinas and Athanasios Kotsakis

Cancers 2026, 18(9), 1463; https://doi.org/10.3390/cancers18091463 - 2 May 2026

Cited by 1 | Viewed by 999

Abstract

Background/Objectives: Advanced prostate cancer (PCa) evolves through adaptive mechanisms that sustain tumor growth despite the suppression of androgen receptor (AR) signaling. Accumulating evidence identifies activation of the hepatocyte growth factor (HGF)/MET pathway as a potential driver of PCa progression in advanced disease states characterized by AR-independence and therapeutic resistance. We review the biological and clinical evidence supporting MET as a context-dependent therapeutic target and discuss its implications for patient selection and combination strategies. Methods: A comprehensive narrative review of preclinical, translational, and clinical studies evaluating MET-directed therapies for PCa was performed. Results: Aberrant activation of the HGF–MET axis is frequently driven by autonomous paracrine and autocrine loops that sustain pathway activation during disease progression. MET overexpression is associated with adverse pathological features, increased tumor aggressiveness, bone metastasis, lineage plasticity, and resistance to AR-targeted treatments. Preclinical studies have demonstrated that AR suppression, tumor hypoxia and tumor–microenvironment interactions promote MET upregulation, supporting AR-independent growth and epithelial-to-mesenchymal transition. Clinical trials of MET inhibitors have shown modest activity as monotherapies, with the most consistent biological effects observed in bone-dominant disease. Recent studies indicate greater therapeutic potential when MET inhibition is incorporated into rational combination strategies targeting complementary molecular pathways. Emerging data further indicate that MET activation characterizes a biologically aggressive, AR-low or neuroendocrine-like disease state. These findings support a transition from empiric use of MET inhibitors toward precision, context-driven therapeutic development. Conclusions: MET is not a universal therapeutic target but defines a clinically relevant subset of aggressive, AR-indifferent PCa. Future development should focus on biomarker-guided patient selection and rational combination strategies. Integration of molecular profiling, imaging, and liquid biopsy approaches will be essential to identify patients most likely to benefit from MET-directed interventions. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery)

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22 pages, 1518 KB

Open AccessReview

Adipokine Metabolic Drivers, Gut Dysbiosis, and the Prostate Microbiome: Novel Pathway Enrichment Analysis of the Adiposity-Based Chronic Disease—Prostate Cancer Network

by Zachary Dovey, Elena Tomas Bort and Jeffrey I. Mechanick

Cancers 2026, 18(2), 206; https://doi.org/10.3390/cancers18020206 - 8 Jan 2026

Cited by 1 | Viewed by 1301

Abstract

Adiposity-Based Chronic Disease (ABCD) is known to increase the risk of aggressive prostate cancer (PCa), recurrent disease after treatment for localized PCa, and PCa mortality. A key mechanistic link contributing to this enhanced risk is chronic inflammation originating from excess white visceral adipose tissue (WAT; VAT) and periprostatic adipose tissue (ppWAT). Contributing to systemic inflammation is gut dysbiosis, which itself may be caused by ABCD as well as background local inflammation (prostatitis), which is common in aging men and may be exacerbated by the urinary microbiome. Investigating the molecular biology driving inflammation and its association with increased PCa risk, a recent paper applied a network and gene set enrichment to adipokine drivers in the ABCD-PCa network. It found prominent roles for MCP-1, IL-1β, and CXCL-1 in addition to confirming the importance of exposure to lipopolysaccharides and bacterial components, corroborating the role of gut dysbiosis. To further unravel the mechanistic links between ABCD and PCa risk, this critical review will discuss the current literature on prominent inflammatory signaling pathways activated in ABCD; the influence of gut dysbiosis, the urinary microbiome, and chronic prostatitis; and current hypotheses on how these domains may result in the development of aggressive PCa over a man’s life. Moreover, we performed a novel pathway enrichment analysis to further evaluate the associations between ABCD, PCa risk, gut dysbiosis, and the prostate microbiome, the results of which were partitioned into extracellular and intracellular signaling pathways. In the extracellular space, novel mechanistic links between gut dysbiosis and MCP-1, IL-1β, CXCL1, and leptin via bacterial pathogen signaling and the intestinal immune network (for IgA production), crucial for gut immune homeostasis, were found. Within the intracellular space, there were downstream signals activating chemokine and type 2 interferon pathways, focal adhesion PI3K/Akt/mTOR pathways, as well as the JAK/STAT, NF-κB, and PI3K/Akt pathways. Overall, these findings point to an emerging molecular pathway for PCa oncogenesis influenced by ABCD, gut dysbiosis, and inflammation, and further research, possibly with lifestyle program-based clinical trials, may discover novel biomarker panels and molecular targeted therapies for the prevention and treatment of PCa. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery)

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Other

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12 pages, 808 KB

Open AccessSystematic Review

Radical Prostatectomy Following Holmium Laser Enucleation of the Prostate (HoLEP): A Systematic Review of Perioperative, Oncological, and Functional Outcomes

by Stamatios Katsimperis, Lazaros Tzelves, Titos Markopoulos, Themistoklis Bellos, Konstantinos Douroumis, Nikolaos Kostakopoulos and Andreas Skolarikos

Cancers 2025, 17(22), 3685; https://doi.org/10.3390/cancers17223685 - 18 Nov 2025

Viewed by 2305

Abstract

Background: The widespread adoption of holmium laser enucleation of the prostate (HoLEP) has led to a growing number of men subsequently diagnosed with localized prostate cancer requiring radical prostatectomy (RP). However, anatomical alterations after HoLEP may increase surgical complexity and affect outcomes. This systematic review aimed to synthesize current evidence on perioperative, oncological, and functional outcomes of RP following HoLEP. Methods: A systematic literature search was conducted in PubMed, CENTRAL, and ClinicalTrials.gov through to September 2025 in accordance with PRISMA 2020 guidelines (PROSPERO CRD420251134483). Eligible studies included patients undergoing RP after HoLEP with reported perioperative, oncologic, or functional data. Methodological quality was assessed using the ROBINS-I tool, and results were synthesized narratively. Results: Eight retrospective studies comprising 202 patients were included. RP after HoLEP was technically feasible across open, laparoscopic, and robotic approaches. Operative time and the need for bladder-neck reconstruction were increased, reflecting post-enucleation fibrosis, but major complication rates (<5%) and blood loss were comparable to primary RP. Oncological outcomes were preserved, with positive surgical margin rates of 6–20% and biochemical recurrence rates of 7–15%, similar to those of primary RP. Functional recovery, particularly urinary continence, was slower initially but generally equivalent at 12 months. Erectile function outcomes were variable but satisfactory when nerve-sparing was feasible. Conclusions: Radical prostatectomy after HoLEP is a technically demanding yet safe procedure that achieves oncologic and long-term functional outcomes comparable to primary prostatectomy. Prior HoLEP should not preclude curative surgical management of prostate cancer, provided the operation is performed by experienced surgeons in high-volume centers. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Prostate Cancer: From Biomarkers to Precision Surgery)

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